Phenylacetylglutaminate (PG) and Phenylacetate (PN) are metabolites of Phenylbutyrate (PB) and are constituents of antineoplaston AS2-1. These are sodium salts of amino acid derivative and carboxylic acid that inhibit...Phenylacetylglutaminate (PG) and Phenylacetate (PN) are metabolites of Phenylbutyrate (PB) and are constituents of antineoplaston AS2-1. These are sodium salts of amino acid derivative and carboxylic acid that inhibit the growth of neoplastic cells without growth inhibitory effect in normal cells. The aim of this study was to identify molecular pathways involved in the anti-proliferative effect of antineoplastons. Using a total human genome microarray we have found that 1) Vitamin D3 upregulated protein (VDUP1) is significantly upregulated in response to PG and PN in the U87 glioblastoma cells;2) Isobologram analysis shows that PG and PN act in an additive or synergistic manner to effectively suppress proliferation of U87 cells;3) PG and PN cause cell cycle arrest, changes in expression of several cell cycle genes and suppress expression and activity of the G2/M checkpoint kinase, CHK1. The multiple cellular targets possibly make these compounds effective anti-proliferative agents. We propose that PG and PN in combination target important cellular pathways and upregulate VDUP1 leading to detachment-induced apoptosis in cancer cells.展开更多
Protein-protein interactions （PPIs） have been widely studied to understand the biological processes or molecular functions associated with different disease systems like cancer. While focused studies on individual c...Protein-protein interactions （PPIs） have been widely studied to understand the biological processes or molecular functions associated with different disease systems like cancer. While focused studies on individual cancers have generated valuable information, global and comparative analysis of datasets from different cancer types has not been done. In this work, we carried out bioinformatic analysis of PPIs corresponding to differentially expressed genes from microarrays of various tumor tissues （belonging to bladder, colon, kidney and thyroid cancers） and compared their associated biological processes and molecular functions （based on Gene Ontology terms）. We identified a set of processes or functions that are common to all these cancers, as well as those that are specific to only one or partial cancer types. Similarly, protein interaction networks in nucleic acid metabolism were compared to identify the common/specific clusters of proteins across different cancer types. Our results provide a basis for further experimental investigations to study protein interaction networks associated with cancer. The methodology developed in this work can also be applied to study similar disease systems.展开更多
文摘Phenylacetylglutaminate (PG) and Phenylacetate (PN) are metabolites of Phenylbutyrate (PB) and are constituents of antineoplaston AS2-1. These are sodium salts of amino acid derivative and carboxylic acid that inhibit the growth of neoplastic cells without growth inhibitory effect in normal cells. The aim of this study was to identify molecular pathways involved in the anti-proliferative effect of antineoplastons. Using a total human genome microarray we have found that 1) Vitamin D3 upregulated protein (VDUP1) is significantly upregulated in response to PG and PN in the U87 glioblastoma cells;2) Isobologram analysis shows that PG and PN act in an additive or synergistic manner to effectively suppress proliferation of U87 cells;3) PG and PN cause cell cycle arrest, changes in expression of several cell cycle genes and suppress expression and activity of the G2/M checkpoint kinase, CHK1. The multiple cellular targets possibly make these compounds effective anti-proliferative agents. We propose that PG and PN in combination target important cellular pathways and upregulate VDUP1 leading to detachment-induced apoptosis in cancer cells.
基金supported by the start-up funds to CG from SUNY-Albanypartly by the Academic Research Enhancement Award(1R15GM080681-01) to CG from NIGMS/NIH
文摘Protein-protein interactions （PPIs） have been widely studied to understand the biological processes or molecular functions associated with different disease systems like cancer. While focused studies on individual cancers have generated valuable information, global and comparative analysis of datasets from different cancer types has not been done. In this work, we carried out bioinformatic analysis of PPIs corresponding to differentially expressed genes from microarrays of various tumor tissues （belonging to bladder, colon, kidney and thyroid cancers） and compared their associated biological processes and molecular functions （based on Gene Ontology terms）. We identified a set of processes or functions that are common to all these cancers, as well as those that are specific to only one or partial cancer types. Similarly, protein interaction networks in nucleic acid metabolism were compared to identify the common/specific clusters of proteins across different cancer types. Our results provide a basis for further experimental investigations to study protein interaction networks associated with cancer. The methodology developed in this work can also be applied to study similar disease systems.
